tbuckley/cabot-search huggingface dataset:
PATH-08. DNA methylation profiling improves routine diagnostics of paediatric CNS tumours: a prospective population-based study
Authors: Elizabeth Schepke, Maja Löfgren, Torsten Pietsch, Thomas Olsson Bontell, Teresia Kling, Anna Wenger, Sandra Ferreyra Vega, Anna Danielsson, Sandor Dosa, Stefan Holm, Anders Öberg, Per Nyman, Marie Eliasson-Hofvander, Per-Erik Sandström, Stefan M Pfister, Birgitta Lannering, Magnus Sabel, Helena Carén
Journal: Neuro-Oncology (2022)

Abstract AIMS: Paediatric brain tumours are rare and establishing a precise diagnosis can be challenging. Analysis of DNA methylation profiles has been shown to be a reliable method to classify central nervous system (CNS) tumours with high accuracy. We aimed to prospectively analyse CNS tumours diagnosed in Sweden, to assess the clinical impact of adding DNA methylation-based classification to standard paediatric brain tumour diagnostics in an unselected cohort. Methods: All CNS tumours diagnosed in children (0-18 years) during 2017-2020 were eligible for inclusion provided sufficient tumour material was available. Tumours were analysed using genome-wide DNA methylation profiling and classified by the MNP brain tumour classifier. The initial histopathological diagnosis was compared to the DNA methylation-based classification. For incongruent results, a blinded re-evaluation was performed by an experienced neuropathologist. Results: 240 tumours with a histopathology-based diagnosis were profiled. A high-confidence methylation score of 0.84 or more was reached in 78% of the cases. In 69%, the histopathological diagnosis was confirmed and for some of these also refined, 6% were incongruent and the re-evaluation favoured the methylation-based classification. In the remaining 3% of cases, the methylation class was non-contributory or could not be predicted. The change in diagnosis would have had a direct impact on the clinical management in 5% of all patients.Conclusions: Integrating DNA methylation-based tumour classification into routine clinical analysis improves diagnostics and molecular information important for treatment decisions. The results from methylation profiling should be interpreted in the context of clinical and histopathological information.
Interreader agreement with Prostate Imaging Reporting and Data System (PI-RADS) Version 2.1 to improve the detection rate of prostate cancer in MRI/TRUS software fusion prostate biopsy
Authors: J. Kim, W.H. Song, D.D. Lee, S.S. Lee, J.K. Nam, H.S. Ryu, T.U. Kim, S.W. Park
Journal: European Urology (2022)
A genomic urine assay to detect urinary tract recurrences in patients with bladder cancer treated with radiotherapy
Authors: F.C. De Jong, I.G. Iflé, D. Kooper, A.C.J. Van Der Made, J.J. De Jong, T.C.M. Zuiverloon, L. Luca Incrocci, W. Van Criekinge, M. Franckena, J.L. Boormans, E.C. Zwarthoff
Journal: European Urology (2022)
Gangrenous, Suppurative, and Exudative Nonperforated Appendicitis—A Distinct Pathology?
Authors: Jillian C. Jacobson, Rachael A. Clark, Dai H. Chung
Journal: JAMA Surgery (2022)

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Dissecting the progression of cardiac dysfunction in tumor-bearing mice
Authors: C Dostal, LP Szabo, C Aioanei, D Abraham, K Zins, L Bakiri, E Wagner, BK Podesser, A Kiss
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: None. Background Cancer patients undergoing heart-related complications result in high incidences of mortality. Nevertheless, it is still not fully understood whether localized tumors affect heart function prior to the onset of cachexia, hence, making the heart more vulnerable for functional abnormalities in later stages of the disease. In addition to analyse heart function, we focus on the expression BCL-2–associated athanogene 3 (BAG3), a co-chaperone protein and Hsp70, which are highly expressed in tumor but decrease in cardiomyocytes (CM) in heart failure (HF). Methods Colon-26 adenocarcinoma cells (C26; n=22) with/without shIL-6 (C26 shIL-6; n=22) were injected subcutaneously into the right flank of 10-11 weeks old BALB/c male mice. Control mice were injected with vehicle (PBS; n=8). Cardiac function was assessed by echocardiography and invasive hemodynamic measurements 10 (early) and 20 (late) days after the injection, respectively. In addition, the expression of BAG3 and Hsp70 were determined by Western blot as well as the extend of cardiac fibrosis was determined by Masson-Goldner's trichrome staining. Results The tumor size was comparable between the two injected groups. However, only C26 group showed a significant loss of subcutaneous fat and skeletal muscle (p&amp;lt;0.05, respectively), suggesting cachexia. Heart weight normalized to tibia length was not changed in the injected groups as compared to controls (day 20). However, left ventricular ejection fraction (LVEF) showed a tendency to decline in the early phase (p~0.08) in both injected group and it reached significance at late stage (p&amp;lt;0.05). Invasive hemodynamic assessment also confirmed the contractile dysfunction, resulting in a decrease in LV systolic pressure and increase of LV end-diastolic pressure (p&amp;lt;0.05, respectively). Importantly, these functional changes in the heart in tumor-bearing mice were associated with a marked reduction in both BAG3 and Hsp70 in the myocardium. Furthermore, there was no sign of cardiac fibrosis in the injected groups. Discussion Our study shows for the first time that tumor rather than cancer cachexia plays a significant maladaptive role in the progression of cardiac dysfunction in a mouse model of C26 injection-induced cachexia. The progression of cardiac contractile dysfunction was associated with a decline in BAG3 and Hsp70 in tumor-bearing mice, suggesting changes of BAG3/Hsp 70 signalling may be a critical component as well as target.
SWK-09. Baseline Survey of Hematology/Oncology/Cellular Therapy Staff/Faculty Perceptions of Palliative Care
Authors: Molly Hemenway, Jennifer Raybin, Melissa Waters
Journal: Neuro-Oncology (2022)

Abstract Recent literature has shown that pediatric oncology patients and families prefer early integration of palliative care, yet the perception persists by staff and providers that palliative care has a negative connotation. We examined the baseline views of staff at our tertiary care center, prior to expansion of a formal palliative care service. We will describe baseline survey results in a diverse group of hematology/oncology/cellular therapy staff/faculty. This quality improvement project was conceived by the unit-based palliative care committee to compare baseline and follow-up survey results. We report the baseline results of a convenience sample of providers with varied roles. A validated survey for staff perception of palliative care found in the literature was utilized. After institutional qualitative review board approval, the survey was emailed to members of the inpatient and outpatient units. Demographic data collected included gender, level of education, role, patient population, length of career globally and locally. Perception of palliative care was evaluated by asking questions regarding 1) overlap with disease focused care, 2) risks/benefits of palliative care, and 3) timing of palliative care consults. Results were tabulated and graphed for dissemination to the unit-based palliative care committee. A follow-up survey is planned after integration of the developing formal palliative care service. Longitudinal comparison with statistical analysis will be completed at that time. Although most participants disagreed that palliative care is not consistent with curative care and that early palliative care does not induce parental anxiety, yet is perceived by the lay public as end-of-life care. Strong agreement was demonstrated with items regarding integration of palliative care early in the disease trajectory to decrease suffering. Participants also predominantly agreed that education for patients/families and staff/faculty would ameliorate misconceptions about palliative care. Future evaluation after increased palliative care penetration will provide comparison data.
Utility of robotic platform for upper and mid ureteric reconstruction: Our experience at MPUH, Nadiad
Authors: A. Singh, N.S S, A.P Parikh, A.P Patil, R.B Batra, P.S Surwase, A.G Ganpule, R.B.S Sabnis, M.R. Desai
Journal: European Urology (2022)
Mutational landscape of DNA damage response deficiency-related genes and its association with immune biomarkers in esophageal squamous cell carcinoma.
Authors: Fei Xu, Zhiming Chen, Gang Chen, Yongjun Zhu, Ji Chen, Feng Miao, Ning Wu, Song Yang, Beibei Mao, Shengzhou Wang
Journal: Journal of Clinical Oncology (2022)

e16100 Background: Esophageal squamous cell carcinoma (ESCC) has limited effective treatment strategies. DNA damage response (DDR) genes are of therapeutic interest in multiple cancer types. This study aimed to depict the landscape of DDR mutations in ESCC and evaluate the association between DDR mutations and known immunotherapy biomarkers. Methods: We recruited 250 Chinese patients with ESCC and performed next-generation sequencing. The DDR status definition was based on the mutational status of any of the 25 DDR core genes. A total of 107 patients underwent a PD-L1 examination. PDL1-H was defined as CPS ≥10. Results: Among the 250 patients, 73 (29.2%) harbored at least one DDR gene mutation and were defined as DDR-mut. Among the six functional DDR pathways, homologous recombination (HR) (12.4%, 31/250) and others (11.6%, 29/250) were the most frequently mutated. DDR-mut patients were significantly associated with higher tumor mutational burden than those in the DDR-wt group ( P = 7.4e-07). Patients with PDL1-H accounted for 21.2% (36/107) of the patients. PDL1-H was more prevalent in DDR-mut than DDR-wt, although the P value did not reach a significant level (40.5% vs. 30%, P = 0.29). Further analysis revealed that BRCA1, one of the most frequently mutated genes in the HR pathway, was significantly associated with PDL1-H ( P = 0.01). Conclusions: Our data revealed a subset of patients with ESCC harbored DDR gene mutations. Patients with these DDR gene mutations are significantly associated with immune biomarkers, implying the potential feasibility of combining DDR agents with immunotherapy in patients with DDR deficiency.
HGG-40. NF1 mosaicism in a CMMRD-patient with a glioblastoma
Authors: Lea Guerrini-Rousseau, Odile Cabaret, Martine Muleris, Dominique Vidaud, Sophie Cotteret, Etienne Rouleau, Tiphaine Adam de Beaumais, Pascale Varlet, Raphael Morscher, Samuel Abbou, Christelle Dufour, Laurence Brugieres, Jacques Grill
Journal: Neuro-Oncology (2022)

Abstract Constitutional Mismatch Repair Deficiency (CMMRD) and Neurofibromatosis type 1 (NF1) are brain tumor predisposing syndromes associated with café-au-lait macules (CALM). Due to this overlap, establishing the differential diagnosis can be difficult, but remains crucial as treatments and surveillance protocols clearly differ for affected patient according to the underlying disease. We reported a girl, with a clinical diagnosis of sporadic NF1 during childhood, who presented a glioblastoma at 16 years-old. Faced with the NF1-like phenotype, diagnosis of CMMRD was suspected because tumor was ultra-hypermutated (228.67 mut/Mb), with a loss of PMS2 expression in both tumor and normal cells. Germline analyses identified a compound heterozygous pathogenic variant (PV) in the PMS2 gene, with an abnormal methylation tolerance test, that confirmed CMMRD. Moreover, a NF1 PV (20% and 9% in blood and saliva samples respectively) was identified compatible with a germline mosaicism. Patient's phenotype was atypical for CMMRD, with a voluminous neurofibroma and ephelids rather observed in NF1. CMMRD oncogenesis is not currently understood, in particular involvement of an NF1 PV, which could arise early from the ultra-hypermutated burden and might explain clinical signs, in particular CALMs. CMMRD diagnosis allowed proposing an adapted genetic counseling and surveillance for the patient and her parents according to the published guidelines due to the major impact on the patient’s oncological risks and prognosis. The best strategy for surveillance of the neurofibroma is still debated due to uncertainties about its risk of degeneration with a CMMRD underlying disease. This observation raises the question of the frequency of mosaic NF1 germline PV in CMMRD-patients and the time of its postzygotic appearance in the context of a biallelic deficit of one of the MMR genes. Combination of these both CMMRD and NF1 germline PVs would be a strong argument for a combination of MEK-inhibitors with immunotherapy.
Combinations of Toll-like receptor 8 agonist TL8-506 activate human tumor-derived dendritic cells
Authors: Mi He, Bhavesh Soni, Petra C Schwalie, Tamara Hüsser, Caroline Waltzinger, Duvini De Silva, Ylva Prinz, Laura Krümpelmann, Samuele Calabro, Ines Matos, Christine Trumpfheller, Marina Bacac, Pablo Umaña, Mitchell P Levesque, Reinhard Dummer, Maries van den Broek, Stephan Gasser
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Dendritic cells (DCs) are professional antigen presenting cells that initiate immune defense to pathogens and tumor cells. Human tumors contain only few DCs that mostly display a non-activated phenotype. Hence, activation of tumor-associated DCs may improve efficacy of cancer immunotherapies. Toll-like receptor (TLR) agonists and interferons are known to promote DC maturation. However, it is unclear if DCs in human tumors respond to activation signals and which stimuli induce the optimal activation of human tumor DCs. Methods We first screened combinations of TLR agonists, a STING agonist and interferons (IFNs) for their ability to activate human conventional DCs (cDCs). Two combinations: TL8-506 (a TLR8 agonist)+IFN-γ and TL8-506+Poly(I:C) (a TLR3 agonist) were studied in more detail. cDC1s and cDC2s derived from cord blood stem cells, blood or patient tumor samples were stimulated with either TL8-506+IFN-γ or TL8-506+Poly(I:C). Different activation markers were analyzed by ELISA, flow cytometry, NanoString nCounter Technology or single-cell RNA-sequencing. T cell activation and migration assays were performed to assess functional consequences of cDC activation. Results We show that TL8-506 synergized with IFN-γ or Poly(I:C) to induce high expression of different chemokines and cytokines including interleukin (IL)-12p70 in human cord blood and blood cDC subsets in a combination-specific manner. Importantly, both combinations induced the activation of cDC subsets in patient tumor samples ex vivo. The expression of immunostimulatory genes important for anticancer responses including CD40 , IFNB1 , IFNL1 , IL12A and IL12B were upregulated on stimulation. Furthermore, chemokines associated with CD8 + T cell recruitment were induced in tumor-derived cDCs in response to TL8-506 combinations. In vitro activation and migration assays confirmed that stimulated cDCs induce T cell activation and migration. Conclusions Our data suggest that cord blood-derived and blood-derived cDCs are a good surrogate to study treatment responses in human tumor cDCs. While most cDCs in human tumors display a non-activated phenotype, TL8-506 combinations drive human tumor cDCs towards an immunostimulatory phenotype associated with Th1 responses on stimulation. Hence, TL8-506-based combinations may be promising candidates to initiate or boost antitumor responses in patients with cancer.
Prevalence of HPV and cytological abnormalities in young women in Almaty, Kazakhstan.
Authors: Raikhan Bolatbekova, Dilyara Kaidarova, Zaure Dushimova, Oxana Shatkovskaya, Alma Zhylkaydarova, Yerlan Kukubassov, Tolkyn Sadykova, Alima Satanova, Orynbassar Bertleuov, Dauren Kaldybekov
Journal: Journal of Clinical Oncology (2022)

e22503 Background: Cervical cancer (CC) is the second most common type of cancer for women worldwide. 99% of cases of CC are associated with high-risk human papillomaviruses (HPV HR). Unfortunately, data on the epidemiology of HPV in Kazakhstan are limited, especially in young kazakhstani women. This study was provided to determine the prevalence of HPV HR and the cytological abnormalities in young Kazakhstani women, which will allow strengthening control in the existing CC screening in this age. Methods: 101 women aged 18-30 years were invited to this cross-sectional study. Women were mentally healthy and did not have a positive human papillomaviruses (HPV) history. Cervical samples for HPV were analyzed with using of Cobas 4800 HPV test. Cytological examination of smears with using the Bethesda terminology system and HPV test were conducted at Kazakh Institute of Oncology and Radiology. Results: The mean age of the study group was 21.0±2.8 years (range 18-30 years). Prevalence of HPV was 11,8% (12 cases). HPV 16 and 18 were the most common type in analyzed cases (5,9%). Cytological abnormalities occurred in 19,8% (20 cases). The Mann-Whitney test of the frequency of cytological abnormalities showed that the ASCUS and LSIL was significantly more found in the group up to 25 years. The HSIL was more common in a group of women 25 years and older and accounted for 1.9 % out of 2 cases (p &lt; 0.05). Conclusions: The results of this study confirm the need for HPV vaccination of adolescent girls and improvement of the existing screening through the inclusion of women to screening from 25 years of age. Changing of CC screening through implementation of HPV screening with cytological triage of HPV - positive of women can reduce the burden of CC in young age in KazakhstanPrevalence of high risk HPV and cytological abnormalities in young women in Almaty, Kazakhstan.
Extracting keyframes of breast ultrasound video using deep reinforcement learning
Authors: Ruobing Huang, Qilong Ying, Zehui Lin, Zijie Zheng, Long Tan, Guoxue Tang, Qi Zhang, Man Luo, Xiuwen Yi, Pan Liu, Weiwei Pan, Jiayi Wu, Baoming Luo, Dong Ni
Journal: Medical Image Analysis (2022)
NURS-02. Incorporating Nurses and Advanced Practice Providers into Clinical Trial Consortiums; results of a multi-institutional survey from the Pacific Pediatric Neuro-Oncology Consortium (PNOC)
Authors: Shannon Raber, Carly Hoffman, Cassie Kline, Michael Prados, Sabine Mueller, Ashley Meyer
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Incorporation of nurses and advanced practice providers (APPs) creates an opportunity to enhance the work of clinical trial consortia in providing care to children with central nervous system tumors enrolled on clinical trials. Within PNOC, nurses and APPs led an effort to engage nurse scientists in collaborative work. A formalized APP and nursing committee confirmed multi-institutional interest for this effort via a widely distributed, electronic survey. OBJECTIVES: The primary aim was to assess the need for a nursing and APP committee by surveying nurses, APPs, physicians, and CRCs across academic institutions within US and international sites. A secondary aim was to explore educational needs of nurses and APPs and establish resources to augment clinical trial protocol initiation and compliance. METHODS: A de-identified, electronic Qualtrics survey was distributed to all PNOC member institutions in Fall 2021. Participants were divided into 3 groups: physicians, nurses or APPs, and CRCs. RESULTS: A total of 68 participants from 20 different institutions completed surveys. All groups confirmed support for a formalized nursing and APP committee within PNOC. Nurses requested education on targeted therapies, specific study protocols, general neuro-oncology information, and late effects. Barriers for nurse participation included lack of dedicated time (50%) and travel funding for conferences (39%). The surveys elicited physicians overwhelmingly identified key needs for APP or nursing involvement in standardizing protocolized care across institutions (100%), education for patients and staff (95%), and protocol development (89%). CONCLUSIONS: Based on multi-institutional survey results, a nursing and APP working group has been established within PNOC. In response to the needs-based survey, the working group provides a quarterly nursing newsletter, offers education sessions and mentorship opportunities, and participates in multi-disciplinary, disease-specific working groups. Future efforts will review the impact of this committee on protocol development and compliance and overall clinical care of pediatric neuro-oncology patients.
MEDB-47. CD4+ T cells restrict medulloblastoma growth and dissemination
Authors: Tanja Eisemann, Robert Wechsler-Reya
Journal: Neuro-Oncology (2022)

Abstract The immune system serves as a powerful defense not only against pathogens and parasites but also against neoplastic cells. Emerging immunotherapies that boost the activity of tumor-reactive immune cells or counteract immune suppressive mechanisms have shown promising effects in certain cancer types. However, the success of immunotherapy for brain tumors has been limited, highlighting the need for a better understanding of the immune microenvironment. Our preliminary studies have shown that T cells critically affect tumor growth in mouse models of the pediatric brain tumor medulloblastoma. In particular, depletion of CD4+ T cells results in more aggressive growth of medulloblastoma cells and allows these cells to metastasize to the spinal cord. To test whether CD4+ T cells can recognize and attack tumor cells directly, we generated MHC class II knockout tumors. Surprisingly, depletion of CD4+ cells still enhanced tumor growth and metastasis. These results suggest that CD4+ T cells regulate medulloblastoma growth independently of MHC II on tumor cells. We hypothesized that CD4+ T cell may not directly kill tumor cells but recruit and activate another effector immune cell type that eliminates tumor cells. As CD4+ T cells have a well-studied helper function for CD8+ T cells, we examined whether their anti-tumoral function relies on the activation of cytotoxic CD8+ T cells. The depletion of CD4+ T cells still resulted in advanced growth of MHC class I-deficient, and thus CD8+ T cell resistant, tumor cells indicating that CD4+ T cells counteract tumor growth in a CD8+ T cell-independent manner. Ongoing studies are aimed at elucidating the mechanisms by which CD4+ T cells regulate medulloblastoma growth, including the antigen-presenting cells that activate them and the effector cells responsible for killing tumor cells. These studies will advance our understanding of the immune microenvironment in medulloblastoma and allow us to design more effective therapies.